Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Fluctuating selection”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,207 records · Page 67Linked to original sources
PubMed1996

Strategy for recombinant multichain protein synthesis: fibrinogen B beta-chain variants as thrombin substrates.

Thrombotic disease has been found in patients with congenital dysfibrinogens that have abnormalities in the amino terminal domain of the fibrinogen B beta-chain. Surprisingly, these fibrinogens are poor substrates for thrombin. In order to examine the molecular basis for this impaired thrombin-fibrinogen interaction, we synthesized three fibrinogens with single amino acid substitutions in this domain: B beta A68T, B beta P70S, and B beta L72S. B beta-chain expression vectors were altered by PCR-directed mutagenesis of the B beta cDNA. The altered vectors were transfected into a Chinese hamster ovary (CHO) cell line that was constructed as a first step in recombinant fibrinogen synthesis, this CHO line synthesizes fibrinogen A alpha- and gamma-chains. More than 86% of the stably selected clones expressed significant levels of fibrinogen, confirming that a two-step strategy permitted efficient synthesis of variant fibrinogens. In large-scale cultures variant fibrinogen accumulation in serum-free medium fluctuated between 1 and 15 micrograms/mL. Normal and variant recombinant fibrinogens were compared to plasma fibrinogens by following the time course of thrombin-catalyzed release of fibrinopeptides. Only the variant B beta A68T, a change identified in a congenital dysfibrinogen, showed significantly impaired kinetics. The rate of fibrinopeptide A release was decreased 27-fold, and the rate of fibrinopeptide B release was decreased 45-fold relative to normal fibrinogen. Fibrinopeptide release was not significantly altered by the substitutions B beta P70S or B beta L72S. These results suggest that B beta residue Ala68 has a novel and critical role in the interaction between thrombin and fibrinogen.

Amino Acid Sequence↗
PubMed1990

Ion permeation through 5-hydroxytryptamine-gated channels in neuroblastoma N18 cells.

Ionic currents induced by 5-hydroxytryptamine (5-HT) in cultured neuroblastoma N18 cells were studied using whole-cell voltage clamp. The response was blocked by 1-10 nM 5-HT3 receptor-specific antagonists MDL 7222 or ICS 205-930, but not by 1 microM 5-HT1/5-HT2 receptor antagonist spiperone or 5-HT2 receptor-specific antagonist ketanserin. These 5-HT3 receptors seem to be ligand-gated channels because the response (a) did not require internal ATP or GTP, (b) persisted with long internal dialysis of CsF (90 mM), A1F4- (100 microM), or GTP gamma S (100 microM), and (c) with ionophoretic delivery of 5-HT developed with a delay of less than 10 ms and rose to a peak in 34-130 ms. Fluctuation analysis yielded an apparent single-channel conductance of 593 fS. The relative permeabilities of the channel for a variety of ions were determined from reversal potentials. The channel was only weakly selective among small cations, with permeability ratios PX/PNa of 1.22, 1.10, 1.01, 1.00, and 0.99 for Cs+, K+, Li+, Na+, and Rb+, and 1.12, 0.79, and 0.73 for Ca2+, Ba2+, and Mg2+ (when studied in mixtures of 20 mM divalent ions and 120 mM N-methyl-D-glucamine). Apparent permeability ratios for the divalent ions decreased as the concentration of divalent ions was increased. Small monovalent organic cations were highly permeant. Large organic cations such as Tris and glucosamine were measurably permeant with permeability ratios of 0.20 and 0.08, and N-methyl-D-glucamine was almost impermeant. Small anions, NO3-, Cl-, and F-, were slightly permeant with permeability ratios of 0.08, 0.04, and 0.03. The results indicate that the open 5-HT3 receptor channel has an effective minimum circular pore size of 7.6 A and that ionic interactions in the channel may involve negative charges near the pore mouth.

Animals↗
PubMed2003

Drug-induced disinhibition in psychiatrically hospitalized children.

OBJECTIVE: To examine rates and predictors of drug-induced behavioral disinhibition (DIBD) in psychiatrically hospitalized children. METHODS: DIBD was examined in 267 children psychiatrically hospitalized for at least 4 weeks. Age, gender, diagnosis, and medication were covariates. DIBD was defined as dramatic increase in aggression identified by increased time-outs while on medicaton. RESULTS: Twenty (7.5%) children met our criteria. Attention deficit hyperactivity disorder, pervasive developmental disorder, and selective serotonin reuptake inhibitor use appeared to increase the risk, and older age and stimulant use decreased the risk of DIBD. However, it was often difficult to distinguish true DIBD from the behavioral fluctuations of these disturbed children. Fifteen percent of children subsequently improved on the same regimen, 40% improved when the offending drug was stopped and another treatment was started, and the remainder had adverse response to many medications. CONCLUSIONS: DIBD is a complex phenomenon that does not lend itself to simple conclusions and requires further study.

Aggression↗
PubMed1998

Circadian variations in cardiovascular function and their relation to the occurrence and timing of cardiac events.

Circadian patterns of risk for cardiac events and their implications for prevention and treatment of cardiovascular conditions are discussed. Sympathovagal tone, a major biological determinant of circadian variation in cardiovascular function, is modulated through circadian patterns of sleep-wake activity. The influence of neurohumoral activity on cardiovascular function is manifested by 24-hour variability in heart rate, blood pressure, and vasomotor tone. Platelet aggregation and plasminogen-activator inhibitor-1 activity peak around the time of awakening. Conversely, endogenous plasminogen activator exhibits a nadir around the time of awakening. Studies of patterns of occurrence of cardiac disorders such as acute myocardial infarction, sudden cardiac death, stroke, and ventricular arrhythmia show an increased occurrence during the period surrounding awakening. These patterns are consistent with observed circadian patterns in cardiovascular function. Diabetes, left ventricular dysfunction, and congestive heart failure may contribute to alterations in patterns of occurrence of cardiac events. Factors such as race, sex, and age may lead to alterations in circadian variation in cardiovascular function. Unusual physical exertion, stress, and anger may act as triggers of an event at any time of day. The circadian patterns of cardiac events follow the natural fluctuations in endogenous physiological processes, with a vulnerable period consistently observed in the early morning; dynamic assessment of markers of cardiovascular function may assist in determining the extent of disease progression and in selecting cardiovascular therapies.

Cardiovascular Diseases↗
PubMed1995

Survival estimates and sample size: what can we conclude?

Attempts to understand aging processes often involve life-span measurements from which a survival curve is constructed and model parameters estimated. The parameter estimates are then compared, and conclusions concerning the underlying biological processes are subsequently deduced, based upon the magnitude of the parameter differences. In this article we discuss the role of sample size and sample fluctuation on the parameter estimates and the profound effect that these factors may play in our arrival at meaningful biological conclusions. We then extend this discussion to examine one methodology that can help select sample sizes for specific parametric survival models.

Aging↗
PubMed1995

Activation of K+ channels by stimulation of metabotropic glutamate receptors.

Single channel potassium currents activated indirectly via stimulation of metabotropic receptors were recorded in cell-attached patches on hippocampal neurones in slices from neonatal rats. When metabotropic receptors in the area outside of the patch are stimulated by glutamate, quisqualate and trans-ACPD, single channel currents appear with a predominant conductance level of about 20 pS. From the reversal potential and substitution of ionic species, we established that the currents are carried by potassium ions. Using selective blockers of ionotropic receptors in conjunction with specific agonists for the metabotropic receptor, it was ascertained that the channel observed is linked to metabotropic receptors. The currents display submaximal conductance states and fluctuate rapidly between evenly-spaced conductance sublevels.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2004

Field theory of propagating reaction-diffusion fronts.

The problem of velocity selection of reaction-diffusion fronts has been widely investigated. While the mean-field limit results are well known theoretically, there is a lack of analytic progress in those cases in which fluctuations are to be taken into account. Here, we construct an analytic theory connecting the first principles of the reaction-diffusion process to an effective equation of motion via field-theoretic arguments, and we arrive at results already confirmed by numerical simulations.

Journal Article↗
PubMed2003

Experimental realization of a quantum spin pump.

We demonstrate the operation of a quantum spin pump based on cyclic radio-frequency excitation of a GaAs quantum dot, including the ability to pump pure spin without pumping charge. The device takes advantage of bidirectional mesoscopic fluctuations of pumped current, made spin dependent by the application of an in-plane Zeeman field. Spin currents are measured by placing the pump in a focusing geometry with a spin-selective collector.

Journal Article↗
PubMed2002

A structural probe of the doped holes in cuprate superconductors.

An unresolved issue concerning cuprate superconductors is whether the distribution of carriers in the CuO2 plane is uniform or inhomogeneous. Because the carriers comprise a small fraction of the total charge density and may be rapidly fluctuating, modulations are difficult to detect directly. We demonstrate that in anomalous x-ray scattering at the oxygen K edge of the cuprates, the contribution of carriers to the scattering amplitude is selectively magnified 82 times. This enhances diffraction from the doped holes by more than 10(3), permitting direct structural analysis of the superconducting ground state. Scattering from thin films of La2CuO4+delta (superconducting transition temperature = 39 K) at temperature = 50 +/- 5 kelvin on the reciprocal space intervals (0,0,0.21) --> (0,0,1.21) and (0,0,0.6) --> (0.3,0,0.6) shows a rounding of the carrier density near the substrate suggestive of a depletion zone or similar effect. The structure factor for off-specular scattering was less than 3 x 10(-7) electrons, suggesting an absence of in-plane hole ordering in this material.

Journal Article↗
PubMed1977

Fosfomycin in treatment of respiratory bacterial infections.

A study was made of 40 patients suffering from clinically and bacteriologically demonstrated bacterial respiratory infections which were all treated with fosfomycin as the only antibiotic. Studies were made of the sensitivity of the isolated organisms and control of the eradicated and selected organisms. Analytical controls were performed on all patients before, during and after treatment. The average dose employed was 60 mg/kg/day, divided into four doses and administered parenterally. The duration of the treatment fluctuated between 6 and 11 days in 87% of the cases. A clinical and bacteriological evaluation was made of the results. The clinical response was satisfactory in 75% of the cases, partial in 7.5% and poor in 17.5%. The bacteriological evolution was satisfactory in 62.5%, partial in 12.5% and poor in 20%. It was not possible to control the evolution in 15% of the patients. The concentrations of the antibiotic were determined in the sputum of 6 patients and fluctuated between 0.6 and 12.9 mug/ml. In no case could any significant disorders be attributed to the antibiotic.

Adolescent↗
PubMed1988

Plasma cortisol and depression in pathological gamblers.

Basal serum cortisol and dexamethasone suppression test (DST) results were studied in 21 pathological gamblers who varied on the Beck Depression Inventory and selected scales of the Minnesota Multiphasic Personality Inventory, which had previously been shown to be related to depression in gamblers. All subjects were suppressors on the DST. There was a significant relationship between fluctuation in 08.00 h and 16.00 h basal cortisol levels and the psychological measures, suggesting a subtype of pathological gambler with potential clinical significance.

Adult↗
PubMed1998

[Persistence of HB vaccine immune protection and response to hepatitis B booster immunization].

OBJECTIVE: To determine the persistence of immune protection of China-made, plasma-derived HBV vaccine in infants and the time table of booster immunization. METHODS: Serological effect of 7-year follow-up study and antibody response of an experimental study on booster were detected using radioimmunoassay. RESULTS: The protective anti-HBs positive rates of 1,018 children, who were vaccinated according to the regimen of three doses of 10 micrograms HBV vaccine, declined from 75.0% during the first two years to 48.2% at 7 years after the first dosages, however, the positive rates for HBsAg and anti-HBc always fluctuated at low frequency. 144 children aged 6 or 7 years old, who received the HBV vaccine in their infancy and were negative for both HBsAg and anti-HBc before booster, were selected from 1,018 children of the follow-up study and boosted with 1 microgram (intradermally) or 2 micrograms (hypodemically) HBV vaccine. Their anti-HBs GMT and anti-HBs positive rate were 190.6 mIU/ml and 89.6% at one month after booster, significantly higher than 14.7 mIU/ml and 54.9% before booster (P < 0.01), and declined back to 25.3 mIU/ml and 75.5% at 12th month; among 65 children with the anti-HBs negative before booster, 40 of them had the level of anti-HBs > or = 100 mIU/ml one month after booster, suggesting the retention of immunological memory in most of them. CONCLUSIONS: No need for revaccination against hepatitis B at 7th year after the initial immunization due to better persistence of immune protection of the vaccine.

Child↗
PubMed2003

[Prevalence and incidence of dementia among the very old. Review of the literature].

BACKGROUND: The increasing number of elderly and very old people observed in France for more than 20 years raises the problem of an expected increase in the prevalence and incidence of dementia in this population. Prevalence and incidence estimates for persons older than 85 years are incomplete and discordant. This information is crucial for organizing future health and social care. OBJECTIVE: Review of literature of prevalence and incidence of dementia for people older than 85 and their link to aging. METHODS: A Medline search has led to a selection of 50 articles. RESULTS: Some studies conclude that there is an exponential relationship of incidence with age; some, a decrease of dementia in the oldest old population. Prevalence estimates in these studies fluctuate between 15 and 40% and incidence between 60 and 100 person-years. CONCLUSION: The variation of prevalence and incidence estimates for 85 and over are partly due to methodological differences and limitations between studies. Further research is needed to include larger samples of persons aged 85 and over and to confirm results where clinical and public health consequences are major issues.

Age Factors↗
PubMed1995

Experience of pergolide in the treatment of Chinese parkinsonian patients with dose-related fluctuations.

BACKGROUND: To improve dose-related fluctuations in patients with Parkinson's disease, the efficacy of pergolide, a long-acting dopamine receptor agonist, was determined. METHODS: Using a stringent diagnostic criterion for Parkinson's disease, 20 patients were selected for a short-term open-label trial, and were divided into three groups based on the accuracy of clinical diagnosis. RESULTS: Nineteen patients completed the study. The mean dosage of pergolide was 2.89 mg per day. The total motor score improved by 34.1% during the "on" period and by 34.8% during the "off" period (p < 0.001). The recorded daily off time decreased from 40.3% to 11.5% (p < 0.001). There was no statistically significant difference in the magnitude of response among different groups of patients; however, patients with shorter duration of illness also received significantly lower dosage of pergolide. Hallucination, worsening of peak-dose dyskinesia, and lowering of blood pressure were major adverse effects. Pergolide could not prevent the occurrence of neuroleptic malignant syndrome in one patient. CONCLUSIONS: Pergolide is very effective for moderate to advanced Parkinson's disease.

Aged↗
PubMed1996

Frequency and time domain studies of the micro-EEG from the brain extracellular space.

In these studies, recordings from the brain extracellular space of cats are considered. Macro and microelectrodes are utilized. Special studies using visual, auditory stimuli and certain drugs are done. Coherence, power phase and partial coherence spectra of wave field potentials and unit potentials are investigated. The electrographic profile of the micro electroencephalogram (EEG) and micro evoked response (ER) of the extracellular space is different than the macropotentials of the macro (EEG) and the macro (ER). The electrographic patterns of the micro (EEG) and the micro (ER) will vary with the microelectrode size, location and the variable microanatomy. There are many single neuron field potentials differentiated in space and time. In these unit fields there are varying electronic interactions varying in space and time. There are patterned inputs varying in space and time. There are fluctuating microfields distributed in overlapping layers, columns, slabs and patches and periaxonal extracellular spaces of the cerebral and cerebellar white matter. In these anatomical situations there are variable, degrees of local and general selective patterns of synchronization with variable direction, and selective spread. The extracellular space micro (EEG) shows complex and dynamic shifts of the micro (EEG) to the macro (EEG) frequencies and tuned macrofields.

Animals↗
PubMed1992

Differential development of beta-endorphin and mu opioid binding sites in mouse brain.

Mouse brains of various ages from embryonal day 14 (E14) to adult were analyzed for opioid receptor binding using the enkephalin analog Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAMGE) and the opiate alkaloid dihydromorphine (DHM) as mu-selective radioligands. Binding parameters were estimated from homologous and heterologous competition binding curves. During the postnatal period, Kd values for [3H]DAMGE did not change but Bmax values (fmol/mg protein) increased 2.7 fold from postnatal day 3 (P3) to P7. Minor receptor density fluctuations were evident from P7 to adult. Similar results were obtained with [3H]DHM. In contrast, estimation of total mu binding sites (fmol/brain) revealed a continuous rise from P3 to the adult. The postnatal developmental profile of total mu binding sites was comparable to the weight gain of mouse brain and the increase in protein content. In contrast, during the same period beta-endorphin immunoreactivity (IR) levels undergo an increase that is inversely proportional to mu opioid receptor Bmax values. [3H]DAMGE binding to E14 membrane preparations was inhibited to a greater extent by Gpp(NH)p than that to P1 or adult. Additional characterization of mu receptors was accomplished by heterologous competition binding assays. IC50 values for beta-endorphin in competition with [3H]DHM and [3H]DAMGE were age dependent and differed for the two radioligands. These results suggest that mu receptor selectivity for mu-specific peptide and alkaloid ligands changes as a function of age.

Amino Acid Sequence↗
PubMed2005

Modulating the DNA affinity of Elk-1 with computationally selected mutations.

In order to regulate gene expression, transcription factors must first bind their target DNA sequences. The affinity of this binding is determined by both the network of interactions at the interface and the entropy change associated with the complex formation. To study the role of structural fluctuation in fine-tuning DNA affinity, we performed molecular dynamics simulations of two highly homologous proteins, Elk-1 and SAP-1, that exhibit different sequence specificity. Simulation studies show that several residues in Elk have significantly higher main-chain root-mean-square deviations than their counterparts in SAP. In particular, a single residue, D69, may contribute to Elk's lower DNA affinity for P(c-fos) by structurally destabilizing the carboxy terminus of the recognition helix. While D69 does not contact DNA directly, the increased mobility in the region may contribute to its weaker binding. We measured the ability of single point mutants of Elk to bind P(c-fos) in a reporter assay, in which D69 of wild-type Elk has been mutated to other residues with higher helix propensity in order to stabilize the local conformation. The gains in transcriptional activity and the free energy of binding suggested from these measurements correlate well with stability gains computed from helix propensity and charge-macrodipole interactions. The study suggests that residues that are distal to the binding interface may indirectly modulate the binding affinity by stabilizing the protein scaffold required for efficient DNA interaction.

Amino Acid Sequence↗